The transforming growth factor-β (TGFβ) superfamily contains a variety of growth factors that share common sequence elements and structural motifs. These proteins are known to exert biological effects on a large variety of cell types in both vertebrates and invertebrates. Members of the superfamily perform important functions during embryonic development in pattern formation and tissue specification and can influence a variety of differentiation processes, including adipogenesis, myogenesis, chondrogenesis, cardiogenesis, hematopoiesis, neurogenesis, and epithelial cell differentiation. Superfamily members have diverse, often complementary effects. By manipulating the activity of a member of the TGFβ family, it is often possible to cause significant physiological changes in an organism. Changes in muscle, bone, cartilage and other tissues may be achieved by increasing or antagonizing signaling that is mediated by an appropriate TGFβ superfamily member.
Naturally occurring proteins often referred to as ligand traps function as extracellular regulators of TGFβ superfamily ligands. Such ligand traps act either in soluble form or attached to the extracellular matrix and typically sequester ligand by binding to epitopes required for receptor activation. One family of ligand traps includes follistatin and follistatin-related proteins, which possess desirable functional activity based on multiple lines of evidence but have proven difficult to use as therapeutic agents. Thus, there is a need for such agents that function as potent regulators of TGFβ superfamily signaling.